Earlier, we have shown that bioinactive growth hormone (GH) is a significant cause for dwarfism and that this may be also associated with other congenital anomalies. The bioinactive GH is equipotent to normal GH in its groww-reaction with antiserum to GH, but is lacking the ability to bind to somatotropic receptors. This grant application aims to study the prevalence of bioinactive GH among the shortest one percentile of children, and to biochemically characterize the circulating variants of GH in these children, viz. molecular weight and isoelectric point using gel-filtration and isoelectric focussing. These variants will be further characterized a) for their immunoreactivity by specific radioimmunoassay using antisera directed against N- and C-termini and the middle regions of the molecule; and b) for their radioreceptor activity using pregnant rabbit liver membrane, cultured human lymphocytes and rat adipocytes. The mode of inheritance of the bioinactive GH will also be studied by compiling family history and by analyzing the serum GH profile of short parents and siblings. We will study the clinical features associated with each type of bioinactive GH as well as the consequences of the treatment of these children with normal human GH.